We have isolated large plaque (lp) mutants of human adenovirus 2 by local mutagenesis of the left 15 percent of the viral genome. The lp mutants are defective in cellular transformation. These mutants are being characterized with regard to mRNAs and proteins synthesized. We will measure the effect of lp-mutant infection on cellular DNA synthesis, induction of plasminogen activator, and cell surface changes in order to understand the defect of lp mutants in inducing cellular transformation. The lp lesion will be mapped by marker transfer and DNA sequence analysis. We propose to further isolate mutants, particularly ts mutants within the transforming genes and other early viral genes involved in viral DNA replication. These mutants will be used to understand virus-induced cellular transformation, viral replication, and regulation of gene expression.